We compared the cardiorespiratory adaptations to exercise of 21 patients with cystic fibrosis (CF) with those of 17 age-, height-, and weight-matched subjects without lung disease. To assess differences in adaptations to exercise in patients with varying severities of pulmonary disease, we grouped them on the basis of their lung function tests results. Exercise consisted of a progressive, incremental cycle ergometer work test. Work load increased every 2 min until the subject could not continue. During exercise, heart rate, and end-tidal and mixed expired O2 and CO2 tensions, minute ventilation (VE), arterial oxygen saturation, and blood pressure were monitored. The patients breathed significantly larger volumes than normal subjects at work loads greater than 0.8 W/kg. Patients with mild, moderate, or seven disease ventilated more per unit of oxygen consumption than did patients with normal pulmonary functions or control subjects. Despite this high total VE, alveolar hypoventilation was observed in the severe groups, as evidenced by elevated end-tidal PCO2, and contributed to aterial desaturation. Resting heart rate was higher in the severe group. The rate of changes in heart rate with increasing work load was the same in all groups. We conclude that the increased VE during exercise was an attempt to maintain alveolar ventilation in the face of increased dead space. The elevated VE was adequate to preserve normal gas exchange in all patients except those with severe lung disease, where CO2 retention and arterial desaturation were observed.